Perinatal Exposure to Delta-9-tetrahydrocannabinol (THC) Alters Goal-Directed Behavior and Dopamine Functioning in Wistar Rats

Rationale : Cannabis use during pregnancy is common as many pregnant women consider cannabis as a safe way to alleviate symptoms associated with pregnancy because it is “natural”. However, clinical evidence links perinatal cannabis exposure to externalizing behavior in offspring. In preclinical research, most studies focus on exposure to the psychoactive constituent of cannabis, delta-9-tetrahydrocannabinol (THC). THC is lipophilic, allowing it to cross the placental barrier and be secreted in maternal milk, thereby exposing the fetus/neonate. Objective : We used operant procedures to measure motivation and impulsivity in adult offspring perinatally exposed to THC. Methods : Dams were orally exposed to 0 or 5 mg/kg/day THC daily from 14 days prior to breeding to postnatal day (PND) 14. Differential reinforcement of high rates (DRH) and differential reinforcement of low rates (DRL) of responding tasks were used to examine motivation and impulsive action. We also measured dopamine (DA) functioning in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) via in vivo fixed potential amperometry in littermates of rats that completed behavioral testing. Results : Perinatal THC exposure decreased reinforcers earned and completed trials during DRL, decreased DRL burst responses, and decreased lever presses and reinforcers (males only) during DRH. However, it had minimal effects on impulsive action during DRL. While THC exposure did not alter baseline DA release in the NAc or mPFC, it did attenuate the dopaminergic response to cocaine in the NAc. Conclusions : These results suggest perinatal exposure to THC can decrease motivation to work for reinforcers during high-effort tasks, and that this “amotivational state” resulting from perinatal THC exposure may be due to reinforcer devaluation.